N6-cyclopentyl-2',3'-O-ethoxymethylene-adenosine | 151563-15-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N6-cyclopentyl-2',3'-O-ethoxymethylene-adenosine
• 英文别名: N⁶-cyclopentyl-2',3'-O-ethoxymethylene-adenosine
• CAS: 151563-15-4
• 化学式: C₁₈H₂₅N₅O₅
• 分子量: 391.427
• InChiKey: OIHAZIGMQUYQDL-WAOLGMKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  112.78
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N6-cyclopentyl-2',3'-O-ethoxymethylene-adenosine 在 4-二甲氨基吡啶 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 75.0h， 生成 5'-O-cyclohexanoyl-N⁶-cyclopentyladenosine
  参考文献：
  名称：

  摘要：

  Purpose. A series of 5 ' -esters of N " -cyclopentyladenosine (CPA) were prepared with the aim to improve stability and bioavailability of selective A(1) agonists. Log P values, stability, affinity, and activity toward human adenosine A, receptors were evaluated.Methods. An appropriate synthetic procedure was adopted to avoid concomitant deamination at position 6. Log P values were obtained by the Mixxor system. The stability of CPA and its 5 ' -ester was evaluated in human plasma and whole blood and analyzed with highperformance liquid chromatography. The affinities to human A, receptor expressed by N-6-cyclohexyladenosine cells were obtained by binding experiments. The activities were evaluated by measurements of the inhibition of forskolin stimulated 3 ' -5 ' -cyclic adenosine monophosphate, performing competitive binding assays.Results. All prodrugs were more lipophilic than CPA, and their hydrolysis, in whole blood and in plasma, was found related, respectively, to the length and hindrance of 5 ' -substituents. Affinity and activity values indicated a very weak interaction toward adenosine A, receptor of the intact prodrugs.Conclusions. We propose 5 ' -esters of CPA, characterized by suitable lipophilicity and elevated degree of stability in physiological fluids, as possible canditates for CPA prodrugs.

  DOI：

  10.1023/a:1011018730459
• 作为产物：
  描述：

  N6-环戊基腺苷酸 、 原甲酸三乙酯 在 三氯乙酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以86%的产率得到N6-cyclopentyl-2',3'-O-ethoxymethylene-adenosine
  参考文献：
  名称：

  腺苷受体前药：强大的，Ar选择性激动剂的衍生物的合成和生物活性。

  摘要：

  强大的腺苷激动剂N6- [4-[[[[[[[[[[[（2-乙酰氨基乙基）氨基]羰基]甲基]苯胺基]羰基]甲基]苯基]腺苷的5'-酯衍生物（N-AcADAC; 1 ）和N6-环戊基腺苷（CPA; 2）制备为前药。烷基酯或碳酸酯（旨在通过增加亲脂性而进入大脑）和1,4-二氢-1-甲基-3-[（吡啶基羰基）氧基]酯均设计为通过氧化还原递送系统集中在大脑中被合成。在5'阻滞形式下，腺苷激动剂在结合试验中对大鼠脑A1-腺苷受体的亲和力大大降低。二氢吡啶前药29在小鼠运动抑制的测定中具有活性，其中腺苷激动剂具有高度抑制作用。通过非中枢神经系统活性腺苷拮抗剂的外周给药，行为抑郁是不可逆的。在测定腺苷的外周作用（即抑制大鼠的脂解作用）时，母体化合物的效价很高，而二氢吡啶前药的效价要低得多。

  DOI：

  10.1002/jps.2600830112